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General Information
Symbol
Hsap\GFAPR79H.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0283570
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-GFAPR79H
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Carried in construct
Cytology
Nature of the lesion
Statement
Reference
UAS regulatory sequences drive expression Hsap\GFAP coding sequences containing the R79H mutation linked to Alexander disease.
Allele components
Product class / Tool use(s)
Encoded product / tool
Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
is ameliorated by NosJF03220
is ameliorated by p5311-1B-1
is exacerbated by NosUAS.cUa
is ameliorated by p53JF02513
is ameliorated by GluRIIBEGFP
is exacerbated by Catn1
is ameliorated by Hsp26UAS.cWa
is ameliorated by Hsp27UAS.cWa
is exacerbated by Sod1n1
is ameliorated by CatUAS.cAa
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference
Over-expression of Hsap\GFAPR79H.Scer\UAS driven in glia by Scer\GAL4repo.PU, Scer\GAL4alrm.PD or Scer\GAL4Mz709 leads to Rosenthal fiber-like inclusion formations in 20 day old flies; flies with expression of Hsap\GFAPR79H.Scer\UAS driven by Scer\GAL4repo.PU show increases in cell death in the brain and increases in seizure frequency. Over-expression of Hsap\GFAPR79H.Scer\UAS driven in glia by Scer\GAL4repo.PU leads to increased cell death in both glia and neurons (cell non-autonomous neurodegeneration).
Expression of Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo does not affect developmental rate or eclosion. Overall brain structure appears normal at 1 day of age, as assayed by haematoxylin and eosin. A TUNEL assay for apoptotic cells does not reveal dying cells at 1 day after eclosion. However, increasing numbers of TUNEL-positive cells are seen as the animals age, indicating severe toxicity. The TUNEL-positive cells are widespread, with no obvious predilection for particular areas of the brain. In the lamina, there is a trend towards decreased numbers of glial cells with advancing age and a significant loss of neurons at 10 and 20 days of age, consistent with a non-autonomous effect. Expression of Hsap\GFAPR79H.Scer\UAS in glial under the control of Scer\GAL4repo promotes the loss of GluRIIB-expressing neurons which is particularly apparent by 20 days after eclosion. Flies expressing Hsap\GFAPR79H.Scer\UAS in glial under the control of Scer\GAL4repo exhibit a significantly increased frequency of seizures in response to mechanical stimulation (with more frequency than in Hsap\GFAPScer\UAS.cWa mutants). Flies expressing Hsap\GFAPR79H.Scer\UAS in glial under the control of Scer\GAL4repo display abnormal protein aggregation, with numerous eosinophilic, elongated and beaded inclusions. These inclusions are present within the cytoplasm of glial cells, as recognised by their characteristic electron-dense cytoplasm. Inclusions are oesinophilic and granular and not membrane bound. Inclusions are present in a widespread pattern throughout the neuropil and cortex. Inclusions are found in 1 day old flies expressing Hsap\GFAPR79H.Scer\UAS. Significant additional accumulation of inclusion bodies occurs by 10 and 20 days of age. Flies expressing Hsap\GFAPR79H.Scer\UAS in glial under the control of Scer\GAL4repo display an increase in autophagy induction with age, with a modest induction present at 1 day after eclosion and more substantial induction at 10 and 20 days of age.
External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Suppressed by
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference
Co-expression of NosScer\UAS.cUa significantly enhances cell death (in both glia and non-autonomously in neurons) and seizure frequency in flies with expression of Hsap\GFAPR79H.Scer\UAS driven by Scer\GAL4repo.PU. Co-expression of NosJF03220 or NosdsRNA.shRNA.Scer\UAS significantly suppresses cell death (in both glia and non-autonomously in neurons) and seizure frequency in flies with expression of Hsap\GFAPR79H.Scer\UAS driven by Scer\GAL4repo.PU. Pharmacological inhibition of Nos through feeding of L-name (compared to no effect seen with feeding of the inactive enantiomer, D-name) decreases cell death and seizure frequency in flies with expression of Hsap\GFAPR79H.Scer\UAS driven by Scer\GAL4repo.PU. Co-expression of p53JF02513 significantly suppresses cell death and seizure frequency in flies with expression of Hsap\GFAPR79H.Scer\UAS driven by Scer\GAL4repo.PU; p5311-1B-1 significantly suppresses cell death.
Overexpression of l(2)eflScer\UAS.cWa in flies expressing Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of l(2)eflScer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies and in activation of autophagy. Overexpression of Hsp26Scer\UAS.cWa in flies expressing Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsp26Scer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies. Overexpression of Hsp27Scer\UAS.cWa in flies expressing Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsp27Scer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies. Overexpression of CatScer\UAS.cAa in flies expressing Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of CatScer\UAS.cAa also decreases the number of seizures. Protection from cellular toxicity does not alter the number of inclusion bodies. A Catn1 heterozygous background significantly enhances Hsap\GFAPR79H.Scer\UAS toxicity and increases the frequency of mechanically-stimulated seizures in these flies. An increase in cellular toxicity does not alter the number of inclusion bodies but does increase autophagy induction. A Sodn1 heterozygous background significantly enhances Hsap\GFAPR79H.Scer\UAS toxicity and increases the frequency of mechanically-stimulated seizures in these flies. Protection from cellular toxicity does not alter the number of inclusion bodies. An increase in cellular toxicity does not alter the number of inclusion bodies but does increase autophagy induction. Overexpression of Hsap\HSPA1AScer\UAS.cWa in flies expressing Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsap\HSPA1AScer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies and in activation of autophagy. Overexpression of Hsap\SOD1Scer\UAS.cWb in flies expressing Hsap\GFAPR79H.Scer\UAS under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsap\SOD1Scer\UAS.cWb also decreases the number of seizures. Protection from cellular toxicity does not alter the number of inclusion bodies. Expression of Eaat1Scer\UAS.cRa significantly suppresses the Hsap\GFAP toxicity, but does not influence inclusion formation, Hsap\GFAP solubility or autophagy induction.
Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\GFAPR79H.Scer\UAS
Hsap\GFAPR79H.UAS
Name Synonyms
Secondary FlyBase IDs
    References (3)